Injectable Anesthetics

Question 1

Anesthetic induction

Answer 1

The process of transitioning into an unconscious state
a very critical phase of an anesthetic procedure
-be well prepared (ET tubes and breathing circuits ready to ensure access to oxygen and inhalation anesthetics within seconds of induction
be focused
administer drugs differently
monitor pt carefully
induction of anesthesia mostly commonly achieved by intravenous route

Question 2

Injectable anesthetics-MOA

Answer 2

Mostly GABA agonists, except for ketamine which is an NMDA receptor antagonist

Question 3

Propofol

Answer 3

the commonest induction drug in small animal practice-required volumes in large animals too huge to be viable
rapid and smooth onset on anesthesia
Short duration of effect (6-15 min)
-effects initially terminated by redistribution from brain to fat tissues and other inactive tissue sites, before eventual liver metabolism
Extrahepatic site of metabolism have been suggested
suitable for C-section anesthesia in small animals
Suitable for maintenance since volume of distribution is large, so it doesnt accumulate much in tissues
-administered by CRI or intermittent boluses for maintenance
Associated with rapid and smooth recovery from anesthesia
-the common induction agent in greyhound dogs, but recoveries also longer compared to other breeds
Lacks analgesic effects

Question 4

Propofol- adverse respiratory effects

Answer 4

induction apnea
-a common adverse effect
-worsened by faster speed of induction and higher doses
-normally lasts a few minutes
-accompanied by cyanosis
-offer IPPV until spontaneous breathing returns
respiratory depression
-respiratory rate and tidal volume decrease

Question 5

Propofol- adverse cardiovascular effects

Answer 5

hypotension (dose dependent)
-peripheral vasodilation (inhibition of alpha-1 adrenoceptors) -> leads to hypotension
should be injected slowly during induction
-induction normally completed in 1-2 min
some negative inotropic effects at high doses
-would also contribute to hypotension
not recommended for severly hemodynamically unstable patients
-use potent opioids with midazolam for these patients
-or use propofol sparingly supplementing anesthesia with opioids and midazolam

Question 6

Propofol in cats

Answer 6

metabolism is slower in cats
-delayed recovery esp after long infusions
may induce hemolysis and heinz body formation

Question 7

Propofol and cranial trauma/surgery cases

Answer 7

an ideal choice for cranial surgery/trauma cases
-does not inc ICP
-dec cerebral oxygen metabolism
Has some anti-epileptic effects
Note: inhalational anesthetics are not recommended in high doses for cranial trauma anesthesia as they affect cerebral vascular autoregulation and may increase ICP

Question 8

Propoflo

Answer 8

An emulsion containing egg lecithin and soybean oil
-does not contain a preservative
-perfect microbial culture medium
Discard within 24 hours of first use to minimize chances of infections in patients

Question 9

Propofol 28

Answer 9

preserved in benzyl alcohol
-makes it potentially unsafe for CRI
stable for up to 28 days

Question 10

Alfaxalone

Answer 10

a neurosteroid-type general anesthetic drug
does not have an effect on glucocorticoid, mineralcorticoid or sex steroid receptors
old formulation contained alphadalone too- an inactive component- withdrawn from market bc histamine release and anaphylactic rxn challenges
New formulation is composed of pure alfaxalone solubilized in cyclo-dextrin
Both IV and IM for induction possible- can be administered IM for sedation of fractious cats/small dogs
Effects mostly similar to propofol
Smooth induction
minimal cardiovascular effects at low doses
Rapid and smooth recovery- 15-25min (dogs): slightly longer acting than propofol
5-10min (cats)
Non-cumulative suitable; for anesthesia IV maintenance by CRI

Question 11

Alfaxalone- adverse respiratory effects

Answer 11

Induction apnea- has potential to cause induction apnea too

Question 12

Alfaxalone summary

Answer 12

probably a safer induction drug than propofol
-adverse effects occur dose dependently; high doses of alfaxalone might compromise vital functions worse than propofol at a modest dose
Still need to be cautious of dose-dependent cardiovascular depression and respiratory depression especially at high doses

Question 13

Etomidate

Answer 13

An imidazole derivative
agonist at GABA receptor
an almost ideal general anesthetic drug
-minimal cardio-pulmonary effects
-cerebral protective 
but causes adrenal (cortisol) suppression days post-operatively 
Fast onset
short periods of unconsciousness (5-10 min)
effects terminated by redistribution from brain to inactive tissues before metabolism by hepatic and plasma esterases
Non-cumulative, but not idea for TIVA
-adrenal (cortisol) suppression
-propylene glycol stabilizing solution
-high osmolality drug preparations
recovery from anesthesia may be rough
muscle tremors; combine with other drugs
not commonly used clinically

Question 14

Etomidate- minimal cardiovascular effects

Answer 14

hardly alters any of the CVS performance indices
safest induction drug of all
used in hemodynamically unstable patients

Question 15

Etomidate- minimal respiratory effects

Answer 15

Induction apnea only at high doses

Question 16

Etomidate and adrenal suppression

Answer 16

When it was first used in humans, anesthetic related mortality inc. deaths bc of adrenal suppression - too little cortisol to mount and effective stress response
though an ideal agent this makes it a concern
avoid CRIs
want to supplement corticosteroids

Question 17

Etomidate- other effects

Answer 17

Excitement and muscle twitching esp during induction
-this has been reported for propofol and alfaxalone too
Pain on injection: propylene glycol and the hyperosmolality
Hemolysis: hyperosmolality

Question 18

Barbiturates: termination of effects

Answer 18

Anesthetic effects are terminated by redistribution from brain before metabolism
redistribution according to how well perfused a tissue is: muscle>fat>bone, tendons and cartilage
Repeated doses or CRIs cause accumulation into the muscle compartment, which later prolong recovery
Cumulative, not recommended for top ups or TIVA

Question 19

Thiopental

Answer 19

Powder form has to be reconstituted just before use
-shelf life of 5 days (it has bacteriostatic properties)
fast onset (faster than propofol) and short duration (about 20 min; longer than propofol)
Irritants due to alkalinity: cellulitis and necrosis if administered perivascularly
Greyhounds: cannot metabolize thiopental quickly enough, therefor contraindicated
Withdrawn form the USA market

Question 20

Thiopental Effects

Answer 20

General anesthesia: induction only-not for maintenance
Poor analgesia
cardiovascular system depression
-hypotension: due mainly to neg inotropy and to some extent to peripheral vasodilation (as with propofol)
-myocardial sensitization to catecholamines: causes arrhythmias
-not suitable for hemodynamically unstable patients
Respiratory depression: induction apnea, bradypnea, low tidal volume
Poor muscle relaxation

Question 21

Ketamine

Answer 21

Dissociative anesthetic

Question 22

Tiletamine

Answer 22

a wildlife capture drug

in asia, commonly used in small animals for induction of anesthesia

Question 23

Dissociatve anesthetics

Answer 23

A state in which there is a functional and electrophysiological dissociation between the the thalamo-cortical systme and the retricular activating system
Characterized by: catalepsy- waxy rigidity of muscles
-eyes remain wide open: apply tear gel
-eye swallowing and laryngeal reflexes persist
-animal anesthetized enough for surgery despite persistent reflexes of the eye and pharynx
Implications: cant easily apply common anesthetic depth monitoring techniques
never administer these drugs alone- always combine with muscle relaxants to reduce muscle tone

Question 24

Ketamine

Answer 24

Can be administered by the intravenous or intramuscular route
MOA not fully understood- NMDA receptor antagonistic action responsible for anesthesia and analgesia; interact with voltage gated calcium channels
onset of action slower than all other induction agents
short duration: 10-20 min of unconsciousness
recovery from anesthesia in small animals can be rough

Question 25

Ketamine analgesia

Answer 25

effect unique to this general anesthetic agent
not as strong as from opioids
good somatic analgesia (skin, muscle)
poor visceral analgesia
prevents wind-up and central sensitization (analgesic for chronic pain)

Question 26

Ketamin- cardiovascular effects

Answer 26

Unique ones:
has indirect sympathomimetic effects from catecholamine release (increased heart rate and blood pressure) in normal healthy hearts
also directly causes cardiac depression (negative inotropy) in diseased hearts

Implications
good for improving cardiac performance in hypotensive, but young and otherwise healthy animals
Contra-indicated in cardiac diseased animals, including geriatrics which are intolerant of any further increased cardiac workload

Question 27

Ketamine-respiratory effects

Answer 27

minor respiratory depression
unlikely to cause induction apnea
-ventilatory response to pCO2 and hypoxia are well maintained
associated with apnestic type breathing
-breath-hold at full inspiration
causes bronchodilation
-reduced airway resistance

Question 28

Ketamine other effects

Answer 28

CNS
inc ICP: due to cerebral vasodilation
inc cerebral oxygen consumption
may cause seizures
inc intra-ocular pressure
Implications
contraindicated in cranial trauma and cranial/spinal space-occupying lesions cases
contraindicated in glaucoma and corneal damage cases

Question 29

Ketamine - metabolism

Answer 29

metabolized by liver mostly
one of the metabolites, norketamine, possibly has anesthetic effects
Norketamine is further metabolized and also partly excreted whole by the kidneys
in cats, ketamine is minimally metabolized and mostly excreted intact be the kidneys
-caution requirement in renal-diseased cats

Question 30

Ketamine- clinical application

Answer 30

always combined with benzos or a2 agonists
common intramuscular anesthetic induction/immobilization in cats
induction (IV) in cats
IM anesthetic induction/immobilization in aggressive dogs
induction IV of anesthesia in hypotensive dogs with healthy myocardium
most common induction agent in horses and cattle-component of triple drip for iv anesthesia
part of analgesic CRI cocktailed used intra operatively and in ICU setting intraoperatively in SA
MLK- morphine, lido, ket
FLK- fentanyl, lido, ket